A POTENTIAL PATHOPHYSIOLOGIC ROLE FOR ALPHA(2)BETA(1)-INTEGRIN IN HUMAN EYE DISEASES INVOLVING VITREORETINAL TRACTION

Cell-mediated contraction of tissues containing fibrillar collagens ca n lead to organ compromise and loss of function. The same process that is biologically advantageous during the contraction phase of wound he aling can be subverted in diseases such as hepatic cirrhosis, pulmonar y fibrosis, and scleroderma, although the cellular and molecular mecha nism of matrix tissue contraction is difficult to study in such chroni c diseases. However, certain human eye diseases that result in tractio nal detachment of the retina and loss of vision are characterized by a cute cell-mediated contraction of collagenous tissue in the vitreous c avity. In this study, we demonstrate that human cells can contract vit reous, a complex biological gel containing type II collagen, in vitro. This cell-mediated contraction can be blocked by antibodies and pepti des that antagonize the function of alpha2beta1 integrin, and the pote ntial for contraction can be conferred upon noncontracting cells by st able transfection of cells with alpha2 cDNA. We also show that this co ntractile process, if focally resisted, can result in remodeling vitre ous from a gel to a structure that resembles a planar membrane, and th at substantial isometric forces can be measured across this tissue. We propose that in diseases such as proliferative diabetic retinopathy a nd proliferative vitreoretinopathy, alpha2beta1 integrin-mediated cont raction of the vitreous and tension at the site of vitreoretinal attac hments contribute to the terminal event of tractional retinal detachme nt. By extension, we propose that alpha2beta1 integrin is a centrally important molecule in human diseases characterized by remodeling and c ontraction of collagenous tissue (i.e., fibrocontractive diseases).